Heat denaturation of hemocytocardiotoxin from the venom of the Central Asian cobra

It has been stated that boiled for three hours haemocytocardiotoxin (HT) from cobra poison loses "direct" hemolytic activity and is unable to potentiate a haemolytic effect of phospholipase A. Surface activity of HT does not change. It is shown that in the course of heat denaturation the aggregation of toxin molecules to dimers and trimers takes place and electrophoretic mobility is decreased. The fluorescence of HT tyroxin residues supported the fact of its irreversible heat denaturation.     

Speech Recognition and In-Vehicle Telematics Devices: Potential Reductions in Driver Distraction

Speech Recognition is frequently cited as a potential remedy to distraction resulting from drivers' operation of in-vehicle devices. This position typically assumes that the introduction of speech recognition will result in reduced cognitive workload and improved driving performance. Past research neither fully supports nor fully discounts this assumption. However, it is difficult to compare many of these studies, due to differences in device operation tasks, the pacing of those tasks, speech recognition system performance, and system interface designs. In an effort to directly address the effect of voice recognition on driver distraction, the present authors developed a capability to manipulate the performance characteristics of a speech recognition system through a Wizard of Oz speech recognition system and installed this system in a simulated driving environment. The sensitivity of the simulated driving environment and speech recognition accuracy manipulation were evaluated in an initial study comparing driver cognitive workload and driving performance during self-paced simulated operation of a personal digital assistant (PDA) during no PDA use, manual control of the PDA, and speech control of the PDA. In the Speech PDA condition, speech recognition accuracy was varied between drivers. Analysis of drivers' emergency braking response times and rated cognitive workload revealed significantly lower cognitive demand and better performance in the No PDA condition when compared to the Manual PDA condition. The Speech PDA condition resulted in response times and rated cognitive workload levels that were between the No PDA and Manual PDA conditions, but not significantly different from either of these conditions. Further analysis of emergency braking performance revealed a non-significant trend towards better performance in conjunction with higher speech recognition accuracy levels. The potential for reducing driver distraction through the careful development and evaluation of speech recognition systems is discussed.     

纳米CaCO3合成及原位改性的研究

在旋转填充床反应器中合成了纳米CaCO3悬浮液,利用pH计跟踪Ca(OH)2碳化反应过程,研究了碳化反应过程原理。结果表明：旋转填充床能极大地强化相间传质与微观混合,提高体系中CaCO3的过饱和度,增大其成核及生长速率。加入适当的添加剂对纳米CaCO3进行原位改性;利用TEM照片研究了原位改性过程中纳米CaCO3的成核生长机理,并考察了添加剂的作用机理。     

Specific Inhibitors of the Breast Cancer Resistance Protein (BCRP)

A new class of specific breast cancer resistance protein (BCRP) inhibitors was identified, showing no inhibition of the ATP binding cassette (ABC) transporters P‐gp and MRP1. Some of these modulators inhibit BCRP with high potency; they are only slightly less potent than Ko143 and could serve as promising lead structures for the design of novel effective BCRP inhibitors. These inhibitors are structurally related to tariquidar (XR9576) and belong to a library of multidrug‐resistance modulators synthesized by our research group. The absence of the tetrahydroisoquinoline substructure appears to play a crucial role for specificity; we found that the presence of this substructure is not essential for interaction with BCRP. To determine the type of interaction between pheophorbide A and compounds with and without the tetrahydroisoquinoline substructure, various substrate pheophorbide A concentrations were used in enzyme kinetics assays. The resulting data show that these compounds share a noncompetitive‐type interaction with pheophorbide A. Experiments with imatinib and pheophorbide A revealed a mixed‐type interaction. The combination of imatinib and compounds with and without the tetrahydroisoquinoline substructure resulted in a positive cooperative effect, indicating that imatinib engages a binding site distinct from that of the new compounds on one side and distinct from that of pheophorbide A on the other side as well. The results of this study suggest that the category of BCRP‐specific inhibitors, which includes only fumitremorgin C, Ko143 and analogues, and novobiocin needs to be extended by this new class of inhibitors, which possess three key characteristics: specificity, potency, and low toxicity.     

Waste disposal and waste avoidance

Waste disposal and waste avoidance are examined from two different perspectives, from the point of view of the waste 'producing' company on the one hand, and from the point of view of the waste disposing company on the other hand. The idea of the basic model lies in the 'turning upside down' of the lot-sizing approach to inventory control theory. We derive a corresponding formula for disposal that shows that the number of waste disposals depends positively on the waste accumulation rate and negatively on the fixed costs for a pick-up. Moreover, we formally work out at which waste avoidance costs a company will enlist the services of a disposal company. Specifically, disposal tends to be preferred to avoidance when waste-avoidance is relatively expensive and three cost rates to be specified are relatively low. Finally, we take the perspective of a monopolistic disposal company that has to decide on the optimal pricing policy. In our model, we determine that the price for a pick-up should be chosen just to cover costs. The disposal company can earn a profit by the suitable choice of the price per unit waste to be disposed of.     

NMDA-receptor antagonists: new pharmacological agents to control the subjective and motivational effects of narcotics]

The effects of N-methyl-D-aspartate. (NMDA) receptor antagonists on the development of long-term adaptation to abused drugs (tolerance, sensitization, dependence) were studied, NMDA receptor antagonists were shown to suppress subjective (including an aversion-motivation component) signs of the opiate withdrawal syndrome and to diminish the secondary reinforcing effects of morphine, cocaine, and electrical brain stimulation rewards of the brain regions. The results obtained indicate the potential efficiency of this new class of pharmacological agents in the context of treatment and prevention of recurrent drug abuse.     

Effects of fibroblast growth factor-2 on longitudinal bone growth

In vivo, fibroblast growth factor-2 (FGF-2) inhibits longitudinal bone growth. Similarly, activating FGF receptor 3 mutations impair growth in achondroplasia and thanatophoric dysplasia. To investigate the underlying mechanisms, we chose a fetal rat metatarsal organ culture system that would maintain growth plate histological architecture. Addition of FGF-2 to the serum-free medium inhibited longitudinal growth. We next assessed each major component of longitudinal growth: proliferation, cellular hypertrophy, and cartilage matrix synthesis. Surprisingly, FGF-2 stimulated proliferation, as assessed by [3H]thymidine incorporation. However, autoradiographic studies demonstrated that this increased proliferation occurred only in the perichondrium, whereas decreased labeling was seen in the proliferative and epiphyseal chondrocytes. FGF-2 also caused a marked decrease in the number of hypertrophic chondrocytes. To assess cartilage matrix synthesis, we measured 35SO4 incorporation into newly synthesized glycosaminoglycans. Low concentrations (10 ng/ml) of FGF-2 stimulated cartilage matrix production, but high concentrations (1000 ng/ml) inhibited matrix production. We conclude that FGF-2 inhibits longitudinal bone growth by three mechanisms: decreased growth plate chondrocyte proliferation, decreased cellular hypertrophy, and, at high concentrations, decreased cartilage matrix production. These effects may explain the impaired growth seen in patients with achondroplasia and related skeletal dysplasias.     

The effect of changing excitation frequency on parallel conductance in different sized hearts

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.     

Suc-Phe-Leu-Phe-SBzl--a new substrate for functional study of Escherichia coli ATP-dependent Lon-proteinase and its modified forms

A new efficient substrate, Suc-Phe-Leu-Phe-SBzl, was proposed for studying the function of the Escherichia coli ATP-dependent Lon protease and its modified forms. The kinetic parameters of hydrolysis of the substrate were determined. The esterase activity of protease Lon was found to be nucleotide-regulated.